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Updated: Jul 2, 2026

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
08:01

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Published on: April 21, 2022

Protein kinase C beta in malignant pleural mesothelioma

Leonardo Faoro1, Sivakumar Loganathan, Maria Westerhoff

  • 1Section of Hematology/Oncology, Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637-1470, USA.

Anti-Cancer Drugs
|September 4, 2008
PubMed

Insights

Enzastaurin, a novel inhibitor, shows preclinical activity against malignant pleural mesothelioma (MPM) by targeting Protein Kinase C beta (PKCbeta). It demonstrated synergistic effects with cisplatin and reduced cancer cell migration, suggesting a potential new therapeutic strategy for MPM.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Malignant pleural mesothelioma (MPM) has limited therapeutic options.
  • Protein Kinase C beta (PKCbeta) plays a role in cellular functions relevant to cancer.
  • Enzastaurin is a novel inhibitor of PKC in clinical development.

Purpose of the Study:

  • To evaluate the expression of PKCbeta in MPM.
  • To assess the in-vitro efficacy of enzastaurin against MPM cells.
  • To investigate the effect of enzastaurin on MPM cell migration and downstream signaling pathways.

Main Methods:

  • PKCbeta expression was analyzed in MPM cell lines and patient tissues using immunoblotting and immunohistochemistry.
  • In-vitro cell growth inhibition assays were performed with enzastaurin, alone and in combination with cisplatin.
  • Cell migration was assessed using wound healing assays, and downstream signaling was studied via immunoblotting.

Main Results:

  • PKCbeta1 was expressed in all evaluated MPM samples, with a trend toward lower survival in patients with higher PKCbeta1 expression.
  • Enzastaurin demonstrated an IC50 of 5 micromol/l against MPM cell lines and showed significant synergy with cisplatin.
  • Enzastaurin treatment reduced MPM cell migration by 59.2%, disrupted F-actin architecture, and decreased phosphorylation of key signaling molecules (AKT, FAK, p130Cas, S6, paxillin).

Conclusions:

  • PKCbeta1 is expressed in the majority of MPM samples, indicating its potential as a therapeutic target.
  • Enzastaurin exhibits preclinical activity against MPM, with synergistic effects when combined with cisplatin.
  • PKCbeta inhibition by enzastaurin may reduce MPM invasiveness by impacting cytoskeletal function.

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